Sunday, 12 January 2020

NIPT::Screening for diag of chromosomal disorders of foetus in preg


Conclusion:- Prenatal  diagnosis is now feasible  from the moment   of conception    onward   . Imaging   techniques   have allowed non invasive   diagnosis   while minimally invasive techniques concentrate on sampling   maternal   blood for fetal cells or markers of feto placental metabolism.
Invasive  techniques   have been   rapidly expanding   and becoming safer  comprising   of  A) chorionic   villus  sampling   B) early amniocentesis or C)  midtrimester   amniocentesis  as well as very early  fetoscopy and umbilical vein   sampling Advances in prenatal  diagnostic   techniques   allow for   earlier more   rapid and more   effective detection of congenital  disorders  Recent   advances  in non invasive   detection  methods such as fetal    ultrasound    and the isolation   of fetal cells in the maternal circulation   allow the intrauterine  diagnosis  of congenital infections and chromosomal  and Mendelian disorders  as well as   hematologic disorders.
We   currently have the potential  to diagnose a number of others for which the opportunity has not yet arisen. If a A)  biochemical B) morphologic  C)  chromosomal or D) genetic:-deoxyribonucleic acid    alternation is known  for a specific condition   and is likely to be expressed in one of the fetal  tissues or secretions attempt    at prenatal diagnosis    is reasonable .

Forget CS /Lap ports!!!! Know what are gene probes???? Development  of specific  gene  probes  ::Diagnosis of inherited   disorders  in utero :--  Our   ability to    detect  the inherited   disorders  in utero   will continue to improve  both in the number of   specific  disorders   successfully diagnosed or excluded  and in the increasingly earlier  stages  of pregnancy  at which    the disorder can be detected. Non invasive  prenatal   testing   and non invasive approach   involves   analysis of   cell  free fetal   DNA  in maternal  plasma   or serum . Another   approach   utilizes fetal cells  within the  maternal circulation   as a source  of fetal DNA. 
Advances in instrumentation have decreased the risk   of the invasive    methods of prenatal diagnosis   and improvement   in non invasive methods  such as maternal  serum screening  may eliminate the need  for invasive procedures  altogether   .

Detection of   useful DNA   polymorphisms linked to  genes for specific   diseases and development  of specific  gene  probes  have   improved  the accuracy  of diagnosis  and reduced the  need   for specific fetal   tissues. The   entire genome of an individual  is present   in each cell   even though    a specific   gene product  may not be   expressed  in that cell. Thus DNA   restriction  endonuclease studies    can be  performed  on amniotic  fluid  cells chorionic  villi fetal cells  in maternal     circulation  and fetal  tissues    with equal  facility.  The usefulness   of prenatal   diagnosis   will always  be limited   by the ability   to detect   pregnancies   at risk. If carrier detection is unavailable   the only way to identify  couples     at risk  for offspring  with an autosomal  recessive  condition  is by the birth   of an affected   child. For autosomal  dominant and X linked   recessive  and dominant conditions new mutations will  continue to occur. As  mentioned previously  screening  of all pregnancies for  all defects  is not possible  now and is unlikely  ever to be feasible  either economically or technically . The   reliability of prenatal  diagnosis  will continue   to depend  upon accurate  diagnosis  in the index case  and upon the availability  of a specific and sensitive test  with no overlap in values between heterozygotes and homozygotes for autosomal  recessive   conditions or between normal and affected fetuses   with autosomal   dominant and X linked  recessive  disorders . Correct  interpretation of test results is subject  to experience recognition  of artifact  and variation  in the expression of a given   disorder in utero.
Prenatal   diagnosis   of aneuploidy   and single gene disorders is usually performed   by collecting fetal samples  through   amniocentesis   or CVS. However   these invasive   procedures   are associated  with some degree   of risk to the  fetus and or mother.

Forget about Modern times”( Modern Times is a 1936 American comedy film written and directed by Charlie Chaplin in which his iconic Little Tramp character struggles to survive in the ).Better think of more modern times  written by, played by & directed by  Dr Srimanta Pal “ . What is happening in MORE  recent times? “.Therefore   in recent years  considerable   effort  has been    made to develop   non invasive  prenatal   testing   and non invasive approach   involves   analysis of   cell  free fetal   DNA  in maternal  plasma   or serum . Another   approach   utilizes fetal cells within the  maternal circulation   as a source  of fetal DNA  .

 In fact   cells and   cffDNA can be found   circulating   in maternal  blood   .Fetal   cells  recovered  from maternal blood   provide  the only source   of pure fetal DNA for NIPT. Fetal   nucleated erythrocytes   are considered  the most suitable  maternally circulating  fetal   cells for  this purpose, because  they are  not commonly found in the peripheral  blood fo  healthy adult and are most   abundant in the fetus during early gestation . Because   fetal cells   in maternal blood   are extremely  rare a definitive  separation  method has  not yet  been established. Fetal   nucleated  erythrocytes can be enriched from maternal blood   via fluorescednce or magnetic activated cell sorting  density gradients  immune magnetic beads or  micromanipulation. Fetal cells   are identified ny  Giemsa staining   hybridization with Y  chromosome specific  probes   polymerase chain reaction detection of a specific  paternal  allele or immune staining  for fetal cell  antigens. Amplification of   fetal DNA    sequences by primer  extension    pre amplification  and PCR has allowed  prenatal   screening  for Duchenne muscular   dystrophy and   the fetal  Rhesus   blood type Sequence  specific  hybridization  has been used to  detect sickle  cell  anemia and beta thalassemia prenatally  in heterozygous   carriers  of these disorders  Thus  at the present   time fetal  gender  and fetal  RgD  blood type   within RhD  negative   pregnant  women can  be  reliably  determined   through  analysis  of  maternal plasma. Furthermore   genetic alterations  can be  diagnosed in the maternal plasma when the  mother does  not have the alterations. However   the diagnosis  of maternally inherited  genetic disease  and aneuploidy  is limited  using  this approach . The use of cffDNA  in maternal plasma  for the diagnosis  of single gene   disorders  is limited  to disorders  caused  by a paternally inherited  gene or a mutation that can  be distinguished  from the maternally  inherited   counterpart . At present fetal gender   can be determined from maternal   plasma. When a pregnant  woman  is a heterozygous   carrier   of an X linked  disorder the determination of fetal gender   is clinically   very informative  for first  step  screening to avoid invasive amniocentesis . noninvasive prenatal   diagnosis of   genetic disorders should be applied   to pregnant women with a  definite   risk for a specific  single  gene disorder . Non invasive   prenatal diagnosis through   examination of intact  fetal cells circulating    within maternal blood   can be used to   diagnose a full range of genetic   disorders . Since   only a limited number of fetal  cells circulate   within maternal blood the above cited procedures to enrich  the cells and enable single   cell analysis with    high sensitivity   are required. Recently   separation  methods including a lectin based  method  and autoimage analyzing  have been  developed  which have     improved the sensitivity of genetic   analysis. This   progress has supported the possibility  of NIPD of genetic disorders .

No comments:

Post a Comment